Identification of lead-produced lipid hydroperoxides in human HepG2 cells and protection using rosmarinic and ascorbic acids with a reference to their regulatory roles on Nrf2-Keap1 antioxidant pathway

Li, Yonghan; Darwish, Wageh Sobhy; Chen, Zhen; Hui, Tan; Wu, Yue; Hirotaka, Suzuki; Chiba, Hitoshi; Hui, Shu-Ping

Identification of lead-produced lipid hydroperoxides in human HepG2 cells and protection using rosmarinic and ascorbic acids with a reference to their regulatory roles on Nrf2-Keap1 antioxidant pathway

Li, Yonghan; Darwish, Wageh Sobhy; Chen, Zhen et al.

Chemico-Biological Interactions, 2019, 314, 108847

Permalink : https://hdl.handle.net/2115/79840

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アクセス権	open access
URI	https://hdl.handle.net/2115/79840
タイトル	Identification of lead-produced lipid hydroperoxides in human HepG2 cells and protection using rosmarinic and ascorbic acids with a reference to their regulatory roles on Nrf2-Keap1 antioxidant pathway
著者	Li, Yonghan ; Darwish, Wageh Sobhy ; Chen, Zhen ; Hui, Tan ; Wu, Yue ; Hirotaka, Suzuki ; Chiba, Hitoshi ; Hui, Shu-Ping
著者名 Li, Yonghan
著者名 Darwish, Wageh Sobhy
著者名 Chen, Zhen
著者名 Hui, Tan
著者名 Wu, Yue
著者名 Hirotaka, Suzuki
e-Rad_Researcher 70197622 著者名 Chiba, Hitoshi
e-Rad_Researcher 90337030 著者名 Hui, Shu-Ping
言語	英語
キーワード	Lead
	HepG2 cells
	Lipid hydroperoxides
	Rosmarinic acid
	Ascorbic acid
	Nrf2
発行日	2019-12-01
出版者	Elsevier
収録物名	Chemico-Biological Interactions
巻(号)	314
ページ	108847
抄録	Lead (Pb) is one of the toxic heavy metals that have several toxicological implications including cytotoxicities and oxidative stress. The release of reactive oxygen species (ROS) usually initiates lipid peroxidation and resulting in inflammation and tissue injury. However, the detailed identification of the Pb-produced lipid hydroperoxides has received little attention. Furthermore, the mechanisms behind such effects are less informed. Therefore, this study firstly investigated Pb-produced lipid hydroperoxides in human HepG2 cells using LC/MS. The effects of Pb on the antioxidant enzymes were additionally examined using qPCR and their dependent activities. As a protection trial, the ameliorative effects of rosmarinic (RMA) and ascorbic (ASA) acids on Pb-induced cytotoxicity and oxidative stress and their regulatory effects on Nrf2/Keap1 pathway were investigated. The achieved results confirmed cytotoxicity and oxidative damage of Pb on HepG2 cells. In addition, 20 lipid hydroperoxides (LOOH) were identified including 11 phosphatidylcholine hydroperoxides (PCOOH), 5 triacylglycerol hydroperoxides (TGOOH) and 4 cholesteryl ester hydroperoxides (CEOOH). The most dominant LOOH species were PCOOH 34:2, PCOOH 34:3, PCOOH 38:7, TGOOH 60:14, TGOOH 60:15, CEOOH 18:3 and CEOOH 20:4. Pb significantly downregulated Nrf2-regulated antioxidant enzymes at both the pretranscriptional and functional levels. Co-exposure of HepG2 cells to RMA and ASA significantly reduced Pb-produced adverse outcomes. This protection occurred via activation Nrf2-Keap1 antioxidant pathway.
資源タイプ	学術雑誌論文
出版タイプ	Accepted Manuscript
権利情報	Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
権利情報	© 2019. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/
PISSN	0009-2797
関連情報	PMID 31610155
関連情報 (isVersionOf)	出版社版DOI https://doi.org/10.1016/j.cbi.2019.108847